Zyprexa: Also a Pain Med?

Meta-analysis suggests analgesic effect for antipsychotic drug

PALM SPRINGS, Calif. -- Olanzapine (Zyprexa) appears to reduce pain, a literature review indicated, and the antipsychotic drug could become a new tool in the battle against pain if confirmed in prospective trials, a researcher said here.

A review of 18 published studies involving use of atypical antipsychotics in patients with a variety of pain states suggested not only that off-label use of these agents has some history, but that olanzapine in particular may be uniquely effective in this context, according to psychiatrist and pain medicine specialist Xavier Jimenez, MD, of the Cleveland Clinic.

Jimenez investigated whether there was evidence for the use of antipsychotics in pain after observing a number of his psychiatric patients experiencing reductions in pain symptoms after starting atypical antipsychotics. The review was done using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), he told MedPage Today in an interview.

Of the 18 studies analyzed, 10 investigated the effects of olazapine on pain, four were of quetiapine, two were of aripiprazole, and one each of risperidone and ziprasidone. Most studies were case series and case reports, but there were a total of three randomized controlled trials.

Several studies reported pain reduction in areas such as chronic pain, cancer, fibromyalgia, and headache. But some had limitations such as low sample size, lack of controls, or other problems.

"Some of the studies were specifically in cancer patients who had exhausted all their other medications. Then they tried one (atypical antipsychotic) and got profound effects. Some palliative doctors and oncologists use these as sort of last ditch resort medications," he said.

Olanzapine has the strongest evidence and the most studies behind it, Jimenez said.

It demonstrated "consistent efficacy in fibromyalgia, and headache and migraine, although only one study (in headache) was a randomized controlled trial with Level 1 evidence," he said. All the other atypical antipsychotics failed to demonstrate efficacy in various pain syndromes and/or lacked robust study designs.

Olanzapine has a variety of actions that could indirectly modulate pain. For one, it modulates histamine; and for another, it also decreases sympathetic tone, which affects pain level.

In addition, studies in rat models demonstrated that olanzapine and risperidone (Risperdal), another atypical antipsychotic, caused analgesia that could be reversed by naloxone.

"That gives us some reverse engineering that maybe there's endogenous opiate activity with these atypical antipsychotics ... Pain is informed not just by your endogenous opiate mechanisms but also other things that modulate pain," Jimenez said.

He noted that doses used in the studies were low. Usually for psychiatric conditions such as psychosis or schizophrenia, doses of 20-30 mg/day of olanzapine might be used. But the pain studies used doses of 2.5-10 mg/day. These lower doses would mean fewer side effects too.

"You're using (atypical antipsychotics) as adjuncts for pain control. So, you get the best of both worlds. You don't have the overwhelming side effects that you get with higher doses, but you have some analgesic effects," he said.

Jimenez said the findings were at least compelling enough to warrant further investigation.

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